tbuckley/cabot-search huggingface dataset:
Assessment of changes in the international prostate symptom score for patients enrolled in a phase I trial of intravesical bacillus Calmette-Guérin combined with intravenous pembrolizumab for recurrent or persistent high-grade non-muscle-invasive bladder cancer after previous bacillus Calmette-Guérin treatment.
Authors: Jazzmyne T. Montgomery, Sherjeel Sana, Ahmed El-Zawahry, James O. Peabody, Tiffany Pearce, Nicole Adams, Mustafa Deebajah, Danuta Dynda, Kara N. Babaian, Jane Crabtree, Kristin Delfino, Kevin McVary, Kathy Robinson, Krishna A. Rao, Shaheen Riadh Alanee
Journal: Journal of Clinical Oncology (2022)

e16553 Background: We conducted the first phase I dose-escalation trial (NCT02324582) of intravesical Bacillus Calmette-Guérin (BCG) in combination with systemic pembrolizumab in patients with high-grade non-muscle-invasive bladder cancer who had persistent or recurrent disease after prior intravesical therapy with BCG. The International Prostate Symptom Score (IPSS) were administered to assess subjects’ urinary bother during the trial. Methods: Eighteen subjects were consented for the study, 13 were treated. The study population was comprised of 11 males, 2 females, with age range 42 - 92 years. The IPSS was assessed at pre-treatment, Week 10 (during combined BCG and pembrolizumab treatment), and at 3 and 6 months from treatment completion. IPSS outcomes were analyzed using a mixed-model repeated measures analysis with p-value &lt; 0.05 considered statically significant. Results: For each time point, there was no significant change in any of the component variables of the IPSS. There was no increase in reported bother symptoms over the course of treatment, given median IPSS scores of 9, 11, 7, and 8 (IQR 1.75) for each time point, respectively. Furthermore, quality of life measurements demonstrated no significant change in subjective burden with 75% of subjects reporting that they were “mostly satisfied” with treatment outcomes, followed by 13% reporting “delighted” or “pleased” at 6 month follow-up. Conclusions: There is no significant change in quality of life or the perceived bother of symptoms indicated in the component variables of the IPSS for our study population before, during or after treatment.
Organ-specific responses to atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma.
Authors: Jaekyung Cheon, Sanghoon Jung, Beodeul Kang, Hyeyeong Kim, Chan Kim, Hongjae Chon
Journal: Journal of Clinical Oncology (2022)

4076 Background: Anti-PD-1 monotherapy elicits various organ-specific immune responses. Although advanced hepatocellular carcinoma (aHCC) showed 20–40% objective response rates (ORR) for cases of extrahepatic lesions in sites such as the lungs or lymph nodes (LNs), only 10% of intrahepatic lesions responded to the monotherapy. The organ-specific responses were due to tumor heterogeneity and differential microenvironments, and may have contributed to the failure of the phase III trials of anti-PD-1 monotherapy for aHCC. Recently, the combination of atezolizumab and bevacizumab (Ate/Bev) as first-line systemic treatment has resulted in survival benefits for patients with aHCC. However, the organ-specific response for this treatment has not been explored. We aimed to evaluate the organ-specific response to Ate/Bev combination therapy in patients with aHCC. Methods: We enrolled patients who received first-line Ate/Bev treatment for aHCC. Eligible patients included those with Child-Pugh A liver function, measurable tumor lesions, and serial image studies available for response evaluation. An independent radiologist reviewed the tumors located in the liver, lungs, LNs, and other sites. Organ-specific response criteria, adapted from RECIST 1.1 and immune-related RECIST, were used. Results: Between May 2020 and June 2021, 124 patients from two Korean cancer referral institutions received first-line Ate/Bev treatment for aHCC. The patient baseline characteristics included: hepatitis B (n = 85, 68.5%), hepatitis C (n = 6, 4.8%), non-viral (n = 33, 26.7%); BCLC stage A/B/C (n = 2, 1.6%/n = 19, 15.3%/n = 103, 83.1%); macrovascular invasion (n = 39, 31.5%); extrahepatic metastasis (n = 75, 60.5%); and AFP &gt;400 ng/ml (n = 39, 31.5%). The median age was 62 years (range: 34–90). With median follow-up duration of 10.1 months, median progression-free survival was 6.8 months (95% CI, 3.6–10.0) and median overall survival was 16.9 months (95% CI, range not available). The ORR was 29.8%. For 260 individual tumor lesions, the liver was the most commonly involved organ (n = 152, 58.5%), followed by the LNs (n = 42, 16.2%) and lungs (n = 24, 9.2%). Ate/Bev treatment induced potent tumor shrinkage in both intrahepatic and extrahepatic lesions: ORR for hepatic lesions was 28.3%; LN lesions, 40.5%; lung lesions, 29.1%; and other metastatic lesions, 19.0%. Further, the organ-specific response rate for intrahepatic tumors decreased as the tumor size increased (36.7%: ≤50 mm, 13.0%: &gt;50 mm). Conclusions: Unlike anti-PD-1 monotherapy, Ate/Bev combination therapy showed favorable responses even in intrahepatic lesions, which are comparable to those in extrahepatic lesions. As such, Ate/Bev may overcome an immune-tolerant hepatic microenvironment in patients with aHCC. (NCT04862949).
CDK4/6 inhibitors outcomes in patients with advanced breast cancer based on HER2-low expression.
Authors: Laura Sabina Lapuchesky, Marcos Bortz, Federico Waisberg, Diego Hernán Enrico, Luisina Ines Bruno, Cristian Alexis Ostinelli, Sergio Gabriel Rivero, Andres Rodriguez, Martin Zarba, Martin Loza, Verónica Yamila Fabiano, Mora Amat, Maria Teresa Pombo, Maria Laura Noro, Federico Andrés Coló, Reinaldo D. Chacon, Matias Rodrigo Chacon, Jorge Carlos Nadal, Adrian Nervo, Maria Victoria Costanzo
Journal: Journal of Clinical Oncology (2022)

1056 Background: HER2-low expression, defined as HER2 immunohistochemistry (IHC) score of 1+ or 2+ with negative in situ hybridization assay (FISH), accounts for 50% of breast cancers. There is limited and conflicting evidence regarding the efficacy of cyclin-dependent kinase (CDK) 4 and 6 inhibitors in patients with ER+ and HER2-low tumors. This study aimed to investigate the prognostic value of HER2-low expression in patients with ER+/HER2-negative advanced breast cancer treated with CDK 4/6 inhibitors. Methods: We retrospectively selected consecutive patients with ER+/HER2-negative advanced breast cancer treated with CDK 4/6 inhibitors plus endocrine therapy in our institution from May 2015 to Feb 2020. Two cohorts were compared, including HER2-0 (IHC score) and HER2-low (HER2 IHC score 1+ and 2+ [negative FISH]) tumors. Comparisons in progression-free survival (PFS) and overall survival (OS) were performed using a log-rank test. The prognostic value of HER2-low was investigated by the Cox regression model. Results: Among the 186 patients included, median age at treatment was 55 (r 27-84), and majority had ECOG 0 (126, 67.8%). Progesterone receptor was positive in 155 (83.3%) tumors. Of note, most patients received CDK4/6 inhibitors and endocrine therapy as first-line setting (131, 70.4%). Mostly received palbociclib (161, 86.6%), while ribociclib and abemaciclib were used in 23 (12.4%) and 2 (1.08%) patients, respectively. Overall, 27 patients (14.5%) had de novo metastatic disease, 68 (36.6%) had only bone metastases, and 69 (37.1%) had visceral disease. Of the total population, 64 (34.4%) tumors were HER2-low (43 [23.1%] HER2-1+, and 21 [11.3%] HER2-2+), and 122 (65.6%) were HER2-0. Median PFS among patients with HER2-0 and HER-low were 19 mo. (95% CI, 13.9-24.1), and 15.6 mo. (95% CI, 11.1-20.0), p = 0.074, respectively. In patients treated with CDK 4/6 in the first-line setting, no statistically significant differences were observed in terms of PFS and OS between HER2-0 and HER2-low (PFS HR 0.73 [95% CI, 0.47-1.13; p = 0.160], and OS HR 1.04 [95% CI, 0.51-2.14; p = 0.909]). Conclusions: In our study, HER2-low expression did not show a statistically significant impact on patients with ER+/HER2-negative advanced breast cancer treated with CDK 4/6 inhibitors. Our study supports the necessity of real-world evidence and the design of pooled analysis to understand the real implication of this biomarker in patients with ER+/HER2-negative tumors.
Frontline therapy of anlotinib combined with carboplatin/paclitaxel and maintenance anlotinib in patients with newly diagnosed advanced ovarian cancer: A phase II, single-arm, multicenter study.
Authors: Yi Jiang, Wenjun Cheng, Yingchun Gao
Journal: Journal of Clinical Oncology (2022)

TPS5607 Background: It has been reported that antiangiogenic drug combined with chemotherapy as first-line treatment, and subsequent antiangiogenic drug as maintenance therapy for ovarian cancer can achieve better clinical benefits. Anlotinib is a highly effective VEGFRs, FGFRs, PDGFRs and c-kit multi-target tyrosine kinase inhibitor which has been approved for the treatment of several solid tumors in China. This single arm, multicentric, phase II study is expected to investigate the efficacy and safety of anlotinib combined with carboplatin/paclitaxel as front-line treatment in patients with advanced ovarian cancer. Methods: Eligible patients with FIGO stage III–IV primary epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer and ECOG PS 0-1 undergo primary debulking surgery or interval debulking surgery, will receive 6-8 cycles of chemotherapy (paclitaxel 175 mg/m2 + carboplatin area under the curve [AUC] 5 q3w) and anlotinib (12 mg po qd, days 1-14, 21 days per cycle, anlotinib will be omitted from the first treatment cycle to prevent delayed wound healing). Anlotinib as maintenance monotherapy will be continue until disease progression, unacceptable toxicity, or death. Patients with prior anti-angiogenic therapy and major surgical procedure within 28 days before the first date of anlotinib therapy will be excluded. This study will recruit approximately 56 patients. The primary endpoint is progression free survival. Key secondary endpoints include overall response rate, disease control rate per RECIST1.1, overall survival, safety. The study began enrolling patients in August 2021 and is ongoing. Clinical trial information: NCT04807166.
Diabetes mellitus and association with outcome in pembrolizumab treated patients with non-small cell lung cancer.
Authors: Yasmin Leshem, Yardenna Dolev, Ido Wolf
Journal: Journal of Clinical Oncology (2022)

e21079 Background: Pembrolizumab and other immune check-point inhibitors became the mainstay of treatment in ample malignancies, including non-small cell lung cancer (NSCLC). Diabetes mellitus (DM) is a highly prevalent chronic metabolic disease. Though DM causes immune dysfunction, the effect of DM on immunotherapy efficacy has not been addressed. Methods: Medical records of consecutive NSCLC patients treated with first-line pembrolizumab alone or combined with chemotherapy at Tel Aviv Medical Center from January 2017 to July 2021 were reviewed. We excluded patients who received a single cycle or were lost to follow-up. Results: Of 234 patients reviewed, 203 were included in the analysis. The median age was 69 years, 128 were men (63%), 152 had adenocarcinoma (75%), 105 received monotherapy pembrolizumab (52%), and 51 patients had DM (25%). Diabetic patients were older (73 vs. 67, p &lt; 0.001) and had a higher mean body index (27 vs. 24, P &lt; 0.001). Median progression free survival (PFS) and overall survival (OS) were significantly shorter in diabetic compared to non-diabetic patients (5.9 vs. 7.1 months, respectively, p = 0.004, and OS 12 vs. 21 months, respectively, p = 0.006). The difference in OS was more pronounced for patients receiving pembrolizumab alone (12 vs. 27 months, p = 0.03), than for those receiving pembrolizumab together with chemotherapy (14.3 vs. 19.4 months, p = 0.06). This suggests that DM is mainly determinantal to anti-tumor immunity and not to the cytotoxic effect of chemotherapy. Multivariate analysis indicated DM as an independent risk factor for inferior PFS (HR 1.7, 95% CI 1.11-2.5, p = 0.014) and OS (HR 1.7, 95% CI 1.09-2.76, p = 0.02). Conclusions: Here we show a potential deleterious effect of DM on the efficacy of pembrolizumab in metastatic NSCLC patients. If further validated, the administration of single agent pembrolizumab in this setting should be reconsidered.
COVID-19 vaccine uptake in patients with cancer and Sars-Cov-2 infection in 2020: Results from the ASCO registry.
Authors: Jen Hanley Hanley Williams, Suanna Steeby Bruinooge, Melinda Kaltenbaugh, Julie R. Gralow, Elizabeth Garrett-Mayer
Journal: Journal of Clinical Oncology (2022)

e18713 Background: The availability of safe and effective COVID-19 vaccines has enabled protections against serious outcomes from SARS-CoV-2 infection. The ASCO Registry provides an opportunity to study the rate of vaccine uptake among patients (pts) with cancer who had SARS-CoV-2 infection prior to availability of vaccines. Methods: Participating US medical oncology practices identify pts eligible for inclusion: pts with a positive SARS-CoV-2 test and, at the same time, either (a) or (b) cancer-free less than 12 months (i.e., in complete remission or post-resection) and receiving adjuvant treatment. Registry data were extracted on 2/4/22. Pts in this analysis had a SARS-CoV-2 positive test between 3/1/2020 and 12/31/2020 and at least one clinical encounter on or after 1/1/21, documenting receipt or not of 1 st and 2 nd vaccine shots. Pts lacking data on vaccination status in their medical records were excluded from analysis. When the exact date of 1 st vaccine shot was known, the primary endpoint was number of days from 1/1/21 to 1 st shot date. If the exact date of 1 st shot was unknown, date was categorized as within 7 days from the clinical encounter, 2-4 weeks, or more than 1 month prior. Summary statistics and 95% confidence intervals (CIs) were calculated using Kaplan-Meier methods. Results: The Registry included 1260 pts with SARS-CoV-2 infection in 2020. Time to vaccination (described using cumulative incidence) across age categories is shown in Table, with 1/1/21 as the baseline. Median time to vaccination ranged from 63 days in the oldest pts (&gt; 80 years of age) to 220 days in the youngest pts (&lt; 45 years of age). Differences in rates of vaccination uptake were most pronounced in the early months (Jan – Mar) and diminished in April and beyond. Conclusions: Older pts with cancer who were infected with SARS-CoV-2 in 2020 received COVID-19 vaccinations in 2021 at higher rates than those of younger ages. Delayed uptake by younger aged pts at outset could be related to lack of clarity on pts with cancer qualifying for early vaccine access and state policies on availability.[Table: see text]
A phase II study of RC48-ADC in HER2-negative patients with locally advanced or metastatic urothelial carcinoma.
Authors: Huayan Xu, Xinan Sheng, Li Zhou, Xieqiao Yan, Siming Li, Zhihong Chi, Chuanliang Cui, Lu Si, Bixia Tang, Lili Mao, Bin Lian, Xuan Wang, Xue Bai, Juan Li, Jun Guo
Journal: Journal of Clinical Oncology (2022)

4519 Background: RC48-ADC is a novel humanized anti-HER2 antibody-drug conjugate (ADC). A phase II clinical study showed that RC48-ADC has a good effect on locally advanced or metastatic urothelial carcinoma with HER2-positive expression that failed standard chemotherapy. In the study, some patients with HER2-postive immunohistochemistry (IHC 2+) but negative FISH test still benefited from the treatment of RC48-ADC.This study was to evaluate the activity and safety of RC48-ADC in HER2-negative patients with locally advanced or metastatic urothelial carcinoma. Methods: This study is an open-label, single-center, single-arm, phase II trial. Eligibility criteria include: histologically confirmed urothelial carcinoma, HER2-negasitive (IHC 0 or 1+), ECOG PS 0-1,and treated with ≥1 prior systemic treatment. Patients received RC48-ADC 2mg/kg q2w until disease progression, unacceptable toxicity, withdrawal of consent, or study termination. The primary objectives were activity (ORR) and safety. Second objectives included progress-free survival, disease control rate and overall survival. Results: As of February 2022(date cutoff),19 patients were enrolled. The median age was 64 years old(range:36-77). At baseline, there were 6 patients with HER2(IHC 0), and 13 patients with HER2(IHC 1+).Most patients (13/19) had visceral metastasis. 15(79%) patients had received≥2 lines treatment.At date cutoff, 19 patients were assessable for response. The objective response rate was 26.3% (95% CI:9.1%,51.2%) and the DCR was 94.7% (18/19). The mPFS was 5.5months (95% CI:3.9,6.8) and mOS was 16.4months (95% CI:7.1,21.7).All of the 6 patients with HER2(0) were SD in the study. The ORRs were 38% (5/13) in patients with HER2(IHC 1+),31% (4/13) in visceral metastasis,17% (1/6) in liver metastasis patients,27% (4/15) in patients post to ≥ 2 lines of treatment. Common treatment-related AEs were leukopenia (52.6%), hypoesthesia (47.4%),alopecia (47.4%), AST increase (42.1%), ALT increase (42.1%), and neutropenia (42.1%), fatigue (42.1%),nausea (26.3%), vomiting (15.8%).Most of these AEs were Grade 1 or 2. The AE of Grade 3 was neutropenia (10.5%). The SAE was CPK increased (5.3%). Conclusions: This study showed that RC48-ADC was safe and the ORR was 26.3% in HER-negative patients with locally advanced or metastatic urothelial carcinoma. The enrollment was completed and data will be updated later. Clinical trial information: NCT04073602.
Genetic abnormalities and aberrant expression of genes involved in chromosome segregation and mitosis in patients with chromosomally unstable malignant soft tissue tumors haboring extensive somatic loss-of-heterozygosity (LOH).
Authors: Katsuhito Takahashi, Yasutomo Miyaji, Hajime Higuchi, Yoshihiro Komohara, Shinsuke Aida, Jun Yashima, Hiromasa Yamamoto, Ken Suzawa, Yuko Takahashi, Shinichi Toyooka, Hiroyuki Narahara, Junko Yotsumoto, Yu Oyama, Yasuo Ono, Satoshi Teraoka
Journal: Journal of Clinical Oncology (2022)

11576 Background: Malignant soft tissue tumor is a rare cancer with few therapeutic options. Recent genomic analysis of soft tissue sarcoma (STS) revealed a high degree of chromosomal instability (CIN) including genome-wide copy number alteration, aneuploidy, whole genome doubling and chromothripsis. In STS patients, we observed extensive somatic LOH, a hallmark of CIN, which is haploid of germline mutations/variants in cancer-related genes. CIN of STS genome implicates abnormalities in chromosome segregation and mitosis. So far, studies on this issue, however, have not been reported in STS patients. Methods: We recruited 155 patients with metastatic/recurrent malignant soft tissue tumors (135 female and 20 male, mean age 51 at analysis, 100 LMS, 19 LPS, 4 ESS, 3 UPS, 3 AS, 3 MPT, 3 GIST and others) with information of familial cancer burden. Whole exome sequencing and analysis were performed in both blood and tumor samples as described in 2018ASCO. KIF18A expression was assessed by immunohistochemistry. Results: Patients with tumors harboring less than 33% somatic LOH in a total of somatic and LOH mutations/variants in 595 COSMIC genes (n = 54) have a better prognosis than those (34-66%, n = 49, 67-100%, n = 52) with tumors harboring more LOH genes (5-year OS; 71% vs 52% or 46%, p = 0.0299, p = 0.0117, respectively). Neither TMB nor MSI status was associated with LOH. Of the genes involved in chromosome segregation and mitosis, we found that a family of ARHGAP genes which play a role in the spindle assembly and Aurora A kinase activation was frequently mutated in both tumor and germline genomes (n = 81 in a total of 155). Damaging ARHGAP mutations/variants in tumors are correlated with higher LOH values (54±3.4%, n = 81 vs. 39±3.3%, n = 74. mean±SE, p = 0.0021) and poor prognosis of patients (5-year OS; 58% n = 81 vs. 41% n = 74, p = 0.0098). We also found that elevated and robust expression of a mitotic kinesin KIF18A in tumors harboring higher LOH and/or damaging ARHGAP mutations/variants (n = 12) but not in lower LOH tumors without ARHGAP mutations/variants (n = 4). Conclusions: This study, for the first time, demonstrates that genetic abnormalities and aberrant expression of genes involved in chromosome segregation and mitosis in patients with malignant soft tissue tumors. The results reveal a novel target of drug discovery for incurable STS because CIN tumor cells are shown to be particularly vulnerable to KIF18A inhibition, while somatic, diploid cells are not.
The prognosis of EGFR complex mutation or co-mutation with tyrosine kinase inhibitor treatment in non-small cell lung cancer.
Authors: Da Jiang, Yuhui Fu, Xinliang Zhou, Ying Li, Yanzhi Cui, Lei Hong, Hui Jin, Ke Shi, Fang Huang, Xue Zhang, Shaoshuang Fan, Wenya Song, Ruoying Deng
Journal: Journal of Clinical Oncology (2022)

e21086 Background: To compare the prognoses of EGFR complex mutation, co-mutation and single mutation with first-line TKI treatment in NSCLC patients. Methods: A retrospective study of 215 patients with EGFR-mutated NSCLC who were admitted to the Department of Medical Oncology, the Fourth Hospital of Hebei Medical University from January 2015 to January 2021, all received first-line EGFR-TKI therapy. According to the type of mutation, they were divided into 48 cases (22.3%) of EGFR single mutation group, 48 cases (22.3%) of complex mutation group, and 142 cases (66.0%) of co-mutation group, of which 23 cases (10.6%) both had complex mutation and co-mutation. The prognoses of the latter two groups were compared with that of the single mutation group respectively. SPSS 26.0 was used to analyze the data, and P &lt; 0.05 indicated the difference was statistically significant. Results: Progression-free survival (PFS): the co-mutation group was shorter than the single mutation group (11.0m vs 13.5m; HR = 1.492, 95%CI: 1.036-2.149; P= 0.030), especially the co-mutation was occurred in TP53 (10.5 m vs 13.0m; HR = 1.665, 95%CI: 1.234-2.248; P= 0.001) or HER family (9.0m vs 12.0m; HR = 2.435, 95%CI: 1.492-3.974; P&lt; 0.001). Overall survival (OS): compared with the single mutation group, complex mutation group (36.5m vs 52.0m; HR = 1.480, 95%CI: 0.821-2.668; P= 0.193), co-mutation group (41.0m vs 52.0m; HR = 1.418, 95%CI: 0.901-2.231; P= 0.131) were not statistically different, but the co-mutation of PTEN pathway significantly reduced OS (24.0m vs 46.0m; HR = 1.884, 95%CI: 1.137 -3.120; P= 0.014). Objective response rate (ORR) and disease control rate (DCR) of first-line EGFR-TKI: single mutation group separately compared with complex mutation group and co-mutation group (ORR: 64.6% vs 6.2% vs 27.4%, P&lt; 0.001; DCR: 100% vs 70.8% vs 91.5%, P &lt; 0.001 and 0.007 respectively). After the first-generation EGFR-TKI treatment and secondary EGFR E20 T790M mutation, the presence or absence of the original sensitive mutation affects the PFS of the first-generation TKI (12.0m vs 11.0m; HR = 1.109, 95%CI:0.739-1.664 ; P= 0.616), PFS of the third-generation TKI (10.0m vs 8.0m; HR = 1.130, 95%CI: 0.717-1.781; P= 0.599) and OS (34.0m vs 44.5m; HR = 0.834, 95%CI: 0.505-1.377; P= 0.478) were not statistically different. Conclusions: EGFR co-mutation is a predictor of poor prognosis in NSCLC patients treated with EGFR-TKI; after first-generation EGFR-TKI resistance, the disappearance of the original sensitive mutation cannot predict the prognosis.